Highly diastereoselective synthesis of trifluoromethyl containing spiro[pyrrolidin-3,2′-oxindoles] from N-2,2,2-trifluoroethylsubstituted isatin imines and β,γ-unsaturated α-keto esters

Abstract

Abstract Inspired by the chemistry and biology of fluorine-containing molecules and pyrrolidinyl spirooxindoles, herein we report a highly diastereoselective [3 + 2] cycloaddition reaction of β,γ-unsaturated α-keto esters and N-2,2,2-trifluoroethylisatin ketimines in the presence of the catalyst DABCO. The process enables efficient incorporation of CF3 groups into pharmaceutically important spiro[pyrrolidin-3,2′-oxindoles], bearing four contiguous stereogenic centers including one tetra substituted carbon, with high efficiency (up to 93% yield and >20:1 diastereomeric ratio). Moreover, using β,γ-unsaturated α-keto esters as the 2C building blocks in this reaction, which are different from other enone substrates such as chalcone and benzalacetone, further expanded their scope of applicability.